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1.  Molecular Phylogenetic Analysis of Ballistoconidium-Forming Yeasts in Trichosporonales (Tremellomycetes): A Proposal for Takashimella gen. nov. and Cryptotrichosporon tibetense sp. nov. 
PLoS ONE  2015;10(7):e0132653.
Bullera species in the Trichosporonales (Tremellomycetes, Agaricomycotina) are phylogenetically distinct from Bullera alba (teleomorph: Bulleromyces albus), the type species of Bullera that belongs to Tremellales. In the present study, the three Bullera species, namely Bullera formosensis, Bullera koratensis and Bullera lagerstroemiae, and Cryptococcus tepidarius belonging to the Trichosporonales are transferred into a new genus Takashimella gen. nov. (MycoBank No. MB 810672) based on sequence analysis of the small subunit (SSU) rRNA gene, the D1/D2 domains of large subunit (LSU) rRNA gene and the ITS+5.8S rRNA gene sequences. In addition, the genus Cryptotrichosporon is emended to accommodate a novel ballistoconidium-forming species of the Trichosporonales, which is named as Cryptotrichosporon tibetense (type strain CGMCC 2.02614T = CBS 10455T). The MycoBank number of this new species is MB 810688.
doi:10.1371/journal.pone.0132653
PMCID: PMC4511645  PMID: 26200459
2.  Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration 
Scientific Reports  2015;5:10535.
Minocycline is a broad-spectrum tetracycline antibiotic. A number of preclinical studies have shown that minocycline exhibits neuroprotective effects in various animal models of neurological diseases. However, it remained unknown whether minocycline is effective to prevent neuron loss. To systematically evaluate its effects, minocycline was used to treat Dicer conditional knockout (cKO) mice which display age-related neuron loss. The drug was given to mutant mice prior to the occurrence of neuroinflammation and neurodegeneration, and the treatment had lasted 2 months. Levels of inflammation markers, including glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule1 (Iba1) and interleukin6 (IL6), were significantly reduced in minocycline-treated Dicer cKO mice. In contrast, levels of neuronal markers and the total number of apoptotic cells in Dicer cKO mice were not affected by the drug. In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis.
doi:10.1038/srep10535
PMCID: PMC4441131  PMID: 26000566
3.  Expression profile of Twist, vascular endothelial growth factor and CD34 in patients with different phases of osteosarcoma 
Oncology Letters  2015;10(1):417-421.
The aim of the present study was to investigate the clinical significance of Twist, vascular endothelial growth factor (VEGF) and CD34 expression in osteosarcoma (OS) in order to elucidate potential therapeutic targets for the treatment of OS. Immunohistochemistry was performed to detect the protein expression of Twist, VEGF and CD34 in OS and osteochondroma (OC) tissues. The ratio of the protein expression of Twist and VEGF in OS and OC tissues as well as at different phases of OS was compared using chi-squared tests. Microvessel density (MVD), as determined by CD34 labeling, in OS and OC tissue as well as at different phases of OS was compared using the Student's t-test. In addition, associations between Twist, VEGF and MVD were assessed using the Spearman's rank correlation test. The results revealed that out of the 32 OS tissues examined, 56.25% exhibited Twist positive expression, 71.88% exhibited VEGF positive expression and the MVD was increased compared with that of the OC tissue. The positive rate of Twist and VEGF expression in phase III OS tissues was significantly increased compared with that in phase I/II OS tissues (Twist: χ2=5.732, P=0.018; VEGF: χ2=7.513, P=0.006). The MVD in phase III OS tissues (31.08±3.36 per field) was significantly higher compared with that of the phase I/II OS tissues (41.2±4.17 per field; t=7.536, P<0.001). Spearman's rank correlation analysis revealed that Twist expression was positively associated with VEGF expression (r=0.371, P=0.002) and with MVD (r=0.393, P=0.001) in OS; in addition, VEGF expression was found to have a positive correlation with MVD (r=0.469, P=0.001). In conclusion, the results of the present study demonstrated that OS tissues exhibited elevated Twist and VEGF expression as well as MVD compared with OC tissue. In addition, metastatic OS (phase III) exhibited an increased positive rate of Twist and VEGF expression as well as MVD values compared with non-metastatic OS (phase I/II). Furthermore associations were detected between Twist and VEGF expression as well as VEGF and MVD. Therefore, inhibition of Twist expression may have potential therapeutic use for the treatment of OS.
doi:10.3892/ol.2015.3246
PMCID: PMC4487166  PMID: 26171042
Twist; vascular endothelial growth factor; CD34; osteosarcoma; metastatic
4.  Association study of genetic variants at newly identified lipid gene TRIB1 with coronary heart disease in Chinese Han population 
Background
Recent genome-wide association studies (GWAS) have identified the variants near TRIB1 gene affecting blood lipid levels. However, the association between the reported variants and risk of coronary heart disease (CHD) was not confirmed.
Methods
We conducted two independent case–control studies. The first study consisted of 300 CHD patients and 300 controls and the second study had 1,332 CHD patients and 2,811 controls. The genotypes of two variants rs3201475 and rs17321515 in TRIB1 were determined by TaqMan assay. The dual-luciferase reporter assay was performed for evaluating the function of the SNP rs3201475.
Results
The statistical analysis indicated that single nucleotide polymorphism (SNP) rs17321515 was replicated to be associated with triglyceride (TG) level, which was also significantly associated with CHD risk when using the stratified analysis after adjusting for conventional risk factors. Compared with GG genotype, AA carriers of SNP rs17321515 had higher risk in males (odds ratio (OR) = 1.28, 95 %CI = 1.01–1.61; P = 0.03) and smokers (OR = 1.41, 95%CI = 1.09–1.88; P = 0.01). We did not find significantly association between genotypes of rs3201475 and CHD risk. In addition, no significant difference was found in the luciferase activity assay of SNP rs3201475.
Conclusions
Our findings indicated that SNP rs17321515 is significantly associated with plasma TG level and the increasing risk of CHD among males and smokers in Chinese, whereas there is no positive association between SNP rs3201475 and CHD risk. Smoking could modify the effects of TRIB1 on CHD risk.
doi:10.1186/s12944-015-0043-0
PMCID: PMC4457977  PMID: 25986010
Genetic variant; Lipid; Coronary heart disease
5.  Aspiration dynamics of multi-player games in finite populations 
On studying strategy update rules in the framework of evolutionary game theory, one can differentiate between imitation processes and aspiration-driven dynamics. In the former case, individuals imitate the strategy of a more successful peer. In the latter case, individuals adjust their strategies based on a comparison of their pay-offs from the evolutionary game to a value they aspire, called the level of aspiration. Unlike imitation processes of pairwise comparison, aspiration-driven updates do not require additional information about the strategic environment and can thus be interpreted as being more spontaneous. Recent work has mainly focused on understanding how aspiration dynamics alter the evolutionary outcome in structured populations. However, the baseline case for understanding strategy selection is the well-mixed population case, which is still lacking sufficient understanding. We explore how aspiration-driven strategy-update dynamics under imperfect rationality influence the average abundance of a strategy in multi-player evolutionary games with two strategies. We analytically derive a condition under which a strategy is more abundant than the other in the weak selection limiting case. This approach has a long-standing history in evolutionary games and is mostly applied for its mathematical approachability. Hence, we also explore strong selection numerically, which shows that our weak selection condition is a robust predictor of the average abundance of a strategy. The condition turns out to differ from that of a wide class of imitation dynamics, as long as the game is not dyadic. Therefore, a strategy favoured under imitation dynamics can be disfavoured under aspiration dynamics. This does not require any population structure, and thus highlights the intrinsic difference between imitation and aspiration dynamics.
doi:10.1098/rsif.2014.0077
PMCID: PMC3973373  PMID: 24598208
aspiration dynamics; multi-player games; evolutionary dynamics
6.  PDGF-BB secreted by preosteoclasts induces CD31hiEmcnhi vessel subtype in coupling osteogenesis 
Nature medicine  2014;20(11):1270-1278.
Osteogenesis during bone modeling and remodeling is coupled with angiogenesis. A recent study shows that the specific vessel subtype, strongly positive for CD31 and Endomucin (CD31hiEmcnhi), couples angiogenesis and osteogenesis. We found that preosteoclasts secrete platelet derived growth factor-BB (PDGF-BB), inducing CD31hiEmcnhi vessels during bone modeling and remodeling. Mice with depletion of PDGF-BB in tartrate-resistant acid phosphatase positive (TRAP+) cell lineage (Pdgfb–/–) show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and CD31hiEmcnhi vessels compared to wild-type mice. In the ovariectomized (OVX) osteoporotic mouse model, concentrations of serum and bone marrow PDGF-BB and CD31hiEmcnhi vessels are significantly decreased. Inhibition of cathepsin K (CTSK) increases preosteoclast numbers, resulting in higher levels of PDGF-BB to stimulate CD31hiEmcnhi vessels and bone formation in OVX mice. Thus, pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a novel therapeutic target for osteoporosis to promote angiogenesis for bone formation.
doi:10.1038/nm.3668
PMCID: PMC4224644  PMID: 25282358
7.  The Histone Acetyltransferase Gcn5 Regulates ncRNA-ICR1 and FLO11 Expression during Pseudohyphal Development in Saccharomyces cerevisiae 
BioMed Research International  2015;2015:284692.
Filamentous growth is one of the key features of pathogenic fungi during the early infectious phase. The pseudohyphal development of yeast Saccharomyces cerevisiae shares similar characteristics with hyphae elongation in pathogenic fungi. The expression of FLO11 is essential for adhesive growth and filament formation in yeast and is governed by a multilayered transcriptional network. Here we discovered a role for the histone acetyltransferase general control nonderepressible 5 (Gcn5) in regulating FLO11-mediated pseudohyphal growth. The expression patterns of FLO11 were distinct in haploid and diploid yeast under amino acid starvation induced by 3-amino-1,2,4-triazole (3AT). In diploids, FLO11 expression was substantially induced at a very early stage of pseudohyphal development and decreased quickly, but in haploids, it was gradually induced. Furthermore, the transcription factor Gcn4 was recruited to the Sfl1-Flo8 toggle sites at the FLO11 promoter under 3AT treatment. Moreover, the histone acetylase activity of Gcn5 was required for FLO11 induction. Finally, Gcn5 functioned as a negative regulator of the noncoding RNA ICR1, which is known to suppress FLO11 expression. Gcn5 plays an important role in the regulatory network of FLO11 expression via Gcn4 by downregulating ICR1 expression, which derepresses FLO11 for promoting pseudohyphal development.
doi:10.1155/2015/284692
PMCID: PMC4398931  PMID: 25922832
8.  A new simplified volume-loaded heterotopic rabbit heart transplant model with improved techniques and a standard operating procedure 
Journal of Thoracic Disease  2015;7(4):653-661.
Background
The classic non-working (NW) heterotopic heart transplant (HTX) model in rodents had been widely used for researches related to immunology, graft rejection, evaluation of immunosuppressive therapies and organ preservation. But unloaded models are considered not suitable for some researches. Accordingly, We have constructed a volume-loaded (VL) model by a new and simple technique.
Methods
Thirty male New Zealand White rabbits were randomly divided into two groups, group NW with 14 rabbits and group VL with 16 rabbits, which served as donors and recipients. We created a large and nonrestrictive shunt to provide left heart a sufficient preload. The donor superior vena cave and ascending aorta (AO) were anastomosed to the recipient abdominal aorta (AAO) and inferior vena cava (IVC), respectively.
Results
No animals suffered from paralysis, pneumonia and lethal bleeding. Recipients’ mortality and morbidity were 6.7% (1/15) and 13.3% (2/15), respectively. The cold ischemia time in group VL is slight longer than that in group NW. The maximal aortic velocity (MAV) of donor heart was approximately equivalent to half that of native heart in group VL. Moreover, the similar result was achieved in the parameter of late diastolic mitral inflow velocity between donor heart and native heart in group VL. The echocardiography (ECHO) showed a bidirectional flow in donor SVC of VL model, inflow during diastole and outflow during systole. PET-CT imaging showed the standard uptake value (SUV) of allograft was equal to that of native heart in both groups on the postoperative day 3.
Conclusions
We have developed a new VL model in rabbits, which imitates a native heart hemodynamically while only requiring a minor additional procedure. Surgical technique is simple compared with currently used HTX models. We also developed a standard operating procedure that significantly improved graft and recipient survival rate. This study may be useful for investigations in transplantation in which a working model is required.
doi:10.3978/j.issn.2072-1439.2015.03.05
PMCID: PMC4419328  PMID: 25973231
Heterotopic heart transplantation (HTX); volume-loaded model (VL model); standard operating procedure
10.  Scrotal Exploration for Testicular Torsion and Testicular Appendage Torsion: Emergency and Reality 
Iranian Journal of Pediatrics  2015;25(1):e248.
Background:
Scrotal exploration is considered the procedure of choice for acute scrotum.
Objectives:
We evaluated the importance of early diagnosis and testicular salvage on the therapeutic outcomes of patients with pediatric testicular torsion (TT) and testicular appendage torsion (TAT) in our geographic area.
Patients and Methods:
We performed a retrospective database analysis of patients who underwent emergency surgery for TT or TAT between January 1996 and June 2009. Patient history, physical examination findings, laboratory test results, color Doppler sonography (CDS) results, and surgical findings were reviewed.
Results:
A total of 65 cases were included in our analysis. Forty-two cases were followed up for at least 3 months. Testicular tenderness was identified as the major clinical manifestation of TT, while only a few patients with TAT presented with swelling. CDS was an important diagnostic modality. The orchiectomy rate was 71% in the TT group.
Conclusions:
Cases of acute scrotum require attention in our area. Early diagnosis and scrotal exploration could salvage the testis or preserve normal function without the need for surgery.
doi:10.5812/ijp.248
PMCID: PMC4505972  PMID: 26199690
Spermatic Cord Torsion; Ultrasonography, Doppler, Transcranial; Decompression
11.  Aspiration dynamics in structured population acts as if in a well-mixed one 
Scientific Reports  2015;5:8014.
Understanding the evolution of human interactive behaviors is important. Recent experimental results suggest that human cooperation in spatial structured population is not enhanced as predicted in previous works, when payoff-dependent imitation updating rules are used. This constraint opens up an avenue to shed light on how humans update their strategies in real life. Studies via simulations show that, instead of comparison rules, self-evaluation driven updating rules may explain why spatial structure does not alter the evolutionary outcome. Though inspiring, there is a lack of theoretical result to show the existence of such evolutionary updating rule. Here we study the aspiration dynamics, and show that it does not alter the evolutionary outcome in various population structures. Under weak selection, by analytical approximation, we find that the favored strategy in regular graphs is invariant. Further, we show that this is because the criterion under which a strategy is favored is the same as that of a well-mixed population. By simulation, we show that this holds for random networks. Although how humans update their strategies is an open question to be studied, our results provide a theoretical foundation of the updating rules that may capture the real human updating rules.
doi:10.1038/srep08014
PMCID: PMC4306144  PMID: 25619664
12.  Transcriptional Consequence and Impaired Gametogenesis with High-Grade Aneuploidy in Arabidopsis thaliana 
PLoS ONE  2014;9(12):e114617.
Aneuploidy features a numerical chromosome variant that the number of chromosomes in the nucleus of a cell is not an exact multiple of the haploid number, which may have an impact on morphology and gene expression. Here we report a tertiary trisomy uncovered by characterizing a T-DNA insertion mutant (aur2-1/+) in the Arabidopsis (Arabidopsis thaliana) AURORA2 locus. Whole-genome analysis with DNA tiling arrays revealed a chromosomal translocation linked to the aur2-1 allele, which collectively accounted for a tertiary trisomy 2. Morphologic, cytogenetic and genetic analyses of aur2-1 progeny showed impaired male and female gametogenesis to various degrees and a tight association of the aur2-1 allele with the tertiary trisomy that was preferentially inherited. Transcriptome analysis showed overlapping and distinct gene expression profiles between primary and tertiary trisomy 2 plants, particularly genes involved in response to stress and various types of external and internal stimuli. Additionally, transcriptome and gene ontology analyses revealed an overrepresentation of nuclear-encoded organelle-related genes functionally involved in plastids, mitochondria and peroxisomes that were differentially expressed in at least three if not all Arabidopsis trisomics. These observations support a previous hypothesis that aneuploid cells have higher energy requirement to overcome the detrimental effects of an unbalanced genome. Moreover, our findings extend the knowledge of the complex nature of the T-DNA insertion event influencing plant genomic integrity by creating high-grade trisomy. Finally, gene expression profiling results provide useful information for future research to compare primary and tertiary trisomics for the effects of aneuploidy on plant cell physiology.
doi:10.1371/journal.pone.0114617
PMCID: PMC4267805  PMID: 25514186
13.  Kinetics of Leptospira interrogans Infection in Hamsters after Intradermal and Subcutaneous Challenge 
Background
Leptospirosis is a zoonosis caused by highly motile, helically shaped bacteria that penetrate the skin and mucous membranes through lesions or abrasions, and rapidly disseminate throughout the body. Although the intraperitoneal route of infection is widely used to experimentally inoculate hamsters, this challenge route does not represent a natural route of infection.
Methodology/Principal Findings
Here we describe the kinetics of disease and infection in hamster model of leptospirosis after subcutaneous and intradermal inoculation of Leptospira interrogans serovar Copenhageni, strain Fiocruz L1-130. Histopathologic changes in and around the kidney, including glomerular and tubular damage and interstitial inflammatory changes, began on day 5, and preceded deterioration in renal function as measured by serum creatinine. Weight loss, hemoconcentration, increased absolute neutrophil counts (ANC) in the blood and hepatic dysfunction were first noted on day 6. Vascular endothelial growth factor, a serum marker of sepsis severity, became elevated during the later stages of infection. The burden of infection, as measured by quantitative PCR, was highest in the kidney and peaked on day 5 after intradermal challenge and on day 6 after subcutaneous challenge. Compared to subcutaneous challenge, intradermal challenge resulted in a lower burden of infection in both the kidney and liver on day 6, lower ANC and less weight loss on day 7.
Conclusions/Significance
The intradermal and subcutaneous challenge routes result in significant differences in the kinetics of dissemination and disease after challenge with L. interrogans serovar Copenhageni strain Fiocruz L1-130 at an experimental dose of 2×106 leptospires. These results provide new information regarding infection kinetics in the hamster model of leptospirosis.
Author Summary
Leptospirosis is the most widespread bacterial infection transmitted from animals to man. Humans are exposed to infection when host animals that harbor the bacteria in their kidneys shed them in their urine. Human infections, caused by the bacterium Leptospira interrogans, frequently result in a life-threatening illness characterized by liver and kidney failure. In the hamster model of leptospirosis, signs of hepatic and renal dysfunction developed on days 6 and 7, respectively, after intradermal and subcutaneous inoculation of L. interrogans. Renal dysfunction was preceded by the development of inflammatory changes and the appearance of large numbers of leptospires in the kidney on day 5. On day 6, animals began to lose weight, became dehydrated, and had elevated numbers of neutrophils circulating in their bloodstream. Importantly, animals inoculated intradermally had lower numbers of bacteria in their liver and kidneys on day 6 than animals inoculated subcutaneously and lower weight loss and circulating neutrophil levels on day 7. These studies show that the hamster model of leptospirosis is similar to human infection and indicate that the route of infection has significant effects on the course of the illness.
doi:10.1371/journal.pntd.0003307
PMCID: PMC4239013  PMID: 25411782
14.  Resveratrol and genistein inhibition of rat isolated gastrointestinal contractions and related mechanisms 
World Journal of Gastroenterology : WJG  2014;20(41):15335-15342.
AIM: To investigate the effects and underlying mechanisms of resveratrol and genistein on contractile responses of rat gastrointestinal smooth muscle.
METHODS: Isolated strips of gastrointestinal smooth muscle from Spraque-Dawley rats were suspended in organ baths containing Kreb’s solution, and the contractility of smooth muscles was measured before and after incubation with resveratrol and genistein, and the related mechanisms were studied by co-incubation with various inhibitors.
RESULTS: Resveratrol and genistein dose-dependently decreased the resting tension, and also reduced the mean contractile amplitude of gastrointestinal smooth muscle. Estrogen receptor blockades (ICI 182780 and tamoxifen) failed to alter the inhibitory effects induced by resveratrol and genistein. However, their effects were attenuated by inhibitions of α-adrenergic receptor (phentolamine), nitric oxide synthase (levorotatory-NG-nitroarginine), ATP-sensitive potassium channels (glibenclamide), and cyclic adenosine monophosphate (SQ22536). In high K+/Ca2+-free Kreb’s solution containing 0.01 mmol/L egtazic acid, resveratrol and genistein reduced the contractile responses of CaCl2, and shifted its cumulative concentration-response curves rightward.
CONCLUSION: Resveratrol and genistein relax gastrointestinal smooth muscle via α-adrenergic receptors, nitric oxide and cyclic adenosine monophosphate pathways, ATP-sensitive potassium channels, and inhibition of L-type Ca2+ channels.
doi:10.3748/wjg.v20.i41.15335
PMCID: PMC4223267  PMID: 25386082
Ca2+ channel; Gastrointestinal; Motility; Phytoestrogen; Smooth muscle
15.  Identification of miRNAs involved in pear fruit development and quality 
BMC Genomics  2014;15(1):953.
Background
MicroRNAs (miRNAs) are a class of small, endogenous RNAs that take part in regulating genes through mediating gene expressions at the post-transcriptional level in plants. Previous studies have reported miRNA identification in various plants ranging from model plants to perennial fruit trees. However, the role of miRNAs in pear (Pyrus bretschneideri) fruit development is not clear. Here, we investigated the miRNA profiles of pear fruits from different time stages during development with Illumina HiSeq 2000 platform and bioinformatics analysis. Quantitative real-time PCR was used to validate the expression levels of miRNAs.
Results
Both conserved and species-specific miRNAs in pear have been identified in this study. Total reads, ranging from 19,030,925 to 25,576,773, were obtained from six small RNA libraries constructed for different stages of fruit development after flowering. Comparative profiling showed that an average of 90 miRNAs was expressed with significant differences between various developmental stages. KEGG pathway analysis on 2,216 target genes of 188 known miRNAs and 1,127 target genes of 184 novel miRNAs showed that miRNAs are widely involved in the regulation of fruit development. Among these, a total of eleven miRNAs putatively participate in the pathway of lignin biosynthesis, nine miRNAs were identified to take part in sugar and acid metabolism, and MiR160 was identified to regulate auxin response factor.
Conclusion
Comparative analysis of miRNAomes during pear fruit development is presented, and miRNAs were proved to be widely involved in the regulation of fruit development and formation of fruit quality, for example through lignin synthesis, sugar and acid metabolism, and hormone signaling. Combined with computational analysis and experimental confirmation, the research contributes valuable information for further functional research of microRNA in fruit development for pear and other species.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-953) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2164-15-953
PMCID: PMC4233070  PMID: 25366381
Pear; Fruit development; High-throughput sequencing; miRNA; Lignin synthesis; Sugar and acid
16.  TAZ promotes epithelial to mesenchymal transition via the upregulation of connective tissue growth factor expression in neuroblastoma cells 
Molecular Medicine Reports  2014;11(2):982-988.
Neuroblastoma (NB) is a neuroendocrine cancer that occurs most commonly in infants and young children. The Hippo signaling pathway regulates cell proliferation and apoptosis, and its primary downstream effectors are TAZ and yes-associated protein 1 (YAP). The effect of TAZ on the metastatic progression of neuroblastoma and the underlying mechanisms involved remain elusive. In the current study, it was determined by western blot analysis that the migratory and invasive properties of SK-N-BE(2) human neuroblastoma cells are associated with high expression levels of TAZ. Repressed expression of TAZ in SK-N-BE(2) cells was shown to result in a reduction in aggressiveness of the cell line, by Transwell migration and invasion assay. In contrast, overexpression of TAZ in SK-N-SH human neuroblastoma cells was shown by Transwell migration and invasion assays, and western blot analysis, to result in epithelial-mesenchymal transition (EMT) and increased invasiveness. Mechanistically, the overexpression of TAZ was demonstrated to upregulate the expression levels of connective tissue growth factor (CTGF), by western blot analysis and chromatin immunoprecipitation assay, while the knockdown of TAZ downregulated it. Furthermore, TAZ was shown by luciferase assay to induce CTGF expression by modulating the activation of the TGF-β/Smad3 signaling pathway. In conclusion, the present study is, to the best of our knowledge, the first to demonstrate that the overexpression of TAZ induces EMT, increasing the invasive abilities of neuroblastoma cells. This suggests that TAZ may serve as a potential target in the development of novel therapies for the treatment of neuroblastoma.
doi:10.3892/mmr.2014.2818
PMCID: PMC4262480  PMID: 25354978
epithelial-to-mesenchymal transition; neuroblastoma; TAZ; connective tissue growth factor; transforming growth factor-β signaling
17.  A Comparative Study of Fast-Track Verus Conventional Surgery in Patients Undergoing Laparoscopic Radical Cystectomy and Ileal Conduit Diversion: Chinese Experience 
Scientific Reports  2014;4:6820.
Fast-track surgery (FTS), which combines various techniques with evidence-based adjustments, is aimed to reduce postoperative morbidity, attenuate surgical stress response, thereby accelerating recovery and shorting length of stay. To further investigate the effectiveness of fast-track surgery, we compared the short-term outcomes of laparoscopic radical cystectomy and ileal conduit diversion for Chinese bladder cancer patients with FTS or with CS in our hospital. Patients with bladder cancer were included and divided into two consecutive groups: CS group and FTS group. Duration to first flatus and regular diet, postoperative hospital days, hospital expense, incidence of complications and postoperative surgical stress response were compared. There was no significant difference between the two groups in age, sex, BMI and postoperative TNM classification. Compared with the CS group, the FTS group had significantly shorter duration to first flatus, time to regular diet, postoperative hospital days and hospital expense, less complications, lower white blood count (WBC) and serum of C-reactive protein (CRP) on postoperative day 5 and 7. Our study indicates that FTS program is safe and efficacious for Chinese patients undergoing laparoscopic radical cystectomy and ileal conduit diversion. It can accelerate recovery, reduce stress action, shorten postoperative hospitals days and reduce hospital expenses.
doi:10.1038/srep06820
PMCID: PMC4212226  PMID: 25352195
18.  Quantitative Trait Loci for Mercury Accumulation in Maize (Zea mays L.) Identified Using a RIL Population 
PLoS ONE  2014;9(9):e107243.
To investigate the genetic mechanism of mercury accumulation in maize (Zea mays L.), a population of 194 recombinant inbred lines derived from an elite hybrid Yuyu 22, was used to identify quantitative trait loci (QTLs) for mercury accumulation at two locations. The results showed that the average Hg concentration in the different tissues of maize followed the order: leaves > bracts > stems > axis > kernels. Twenty-three QTLs for mercury accumulation in five tissues were detected on chromosomes 1, 4, 7, 8, 9 and 10, which explained 6.44% to 26.60% of the phenotype variance. The QTLs included five QTLs for Hg concentration in kernels, three QTLs for Hg concentration in the axis, six QTLs for Hg concentration in stems, four QTLs for Hg concentration in bracts and five QTLs for Hg concentration in leaves. Interestingly, three QTLs, qKHC9a, qKHC9b, and qBHC9 were in linkage with two QTLs for drought tolerance. In addition, qLHC1 was in linkage with two QTLs for arsenic accumulation. The study demonstrated the concentration of Hg in Hg-contaminated paddy soil could be reduced, and maize production maintained simultaneously by selecting and breeding maize Hg pollution-safe cultivars (PSCs).
doi:10.1371/journal.pone.0107243
PMCID: PMC4161392  PMID: 25210737
19.  Application of piezoelectric nanogenerator in medicine: bio-experiment and theoretical exploration 
Journal of Thoracic Disease  2014;6(9):1300-1306.
Background
A large number of wearable and implantable electronic medical devices are widely used in clinic and playing an increasingly important role in diagnosis and treatment, but the limited battery capacity restricts their service life and function expansion. Piezoelectric nanogenerators can convert mechanical energy into electrical energy. Our experiment tries to find out if the piezoelectric nanogenerator fixed to the surface of the heart can convert the natural contractions and relaxations of the heart into stable electric energy for electronic medical devices such as pacemakers.
Methods
We used Chinese miniature pig and prepared with standard open chest procedure. Then we fixed two opposite edges of the rectangular nanogenerator at the following three positions of the heart respectively to detect the electric voltage output: Position A, right ventricular surface, near the atrioventricular groove, parallel to the long axis of the heart; Position B, right ventricular surface, parallel to the atrioventricular groove; and Position C, left ventricular surface, near cardiac apex, parallel to the left anterior descending branch. Then we selected the place which has the highest voltage output to fix both ends of the nanogenerator and closed the chest of pig. We recorded the voltage output of nanogenerator under closed chest condition (natural condition) and compared the result with open chest condition. Finally we used Dopamine (positive inotropic agents) and Esmolol (negative inotropic agents) respectively to detect the relation between voltage output of nanogenerator and myocardial contractility.
Results
With its both ends fixed on the surface of the heart, the piezoelectric nanogenerator produced stable voltage output from the mechanical contractions of the heart. Piezoelectric nanogenerator which was fixed at Position A produced the highest voltage output (3.1 V), compared with those fixed at Position B or Position C. The voltage is enough for the pacemaker’s operation. The voltage output of piezoelectric nanogenerator at the natural condition (closed chest) was the same as the open chest condition and made a light emitting diode (LED) light continue to shine, which further confirmed its clinical application value. The voltage output of piezoelectric nanogenerator is positively correlated with the myocardial contractile force. The voltage output increased after we used positive inotropic agents and decreased after we used negative inotropic agents.
Conclusions
Piezoelectric nanogenerators can convert the kinetic energy of the heart during the contractions and relaxations of the muscles to electric energy. The output voltage was stable in three positions on the surface of the heart. The highest voltage appeared on the surface of right ventricle, near atrioventricular groove, parallel to the long axis direction of the heart, which can be the potential new energy source for pacemakers. Piezoelectric nanogenerator can be used as cardiac function monitor in the future for its voltage output is positively correlated with myocardial contractile force.
doi:10.3978/j.issn.2072-1439.2014.09.03
PMCID: PMC4178096  PMID: 25276373
Implantable medical electronic device; wearable medical electronic device; piezoelectric nanogenerator; body mechanical energy; biomechanical energy harvester; new power source
20.  Randomized testing of taste discrimination in a case of congenital aglossia 
Aims
Isolated Congenital Aglossia (ICA) is a rare syndrome where an individual is born without a tongue. A few anecdotal reports have identified taste as a sensation experienced by the person with congenital aglossia (PWCA). To date no systematic investigations have been reported. This study aimed to systematically determine gustatory function in a PWCA.
Methods
The current study utilized a randomized, double-blinded, controlled trial that tested the five basic tastes: sweet (sucrose), sour (acetic acid), salty (sodium chloride), bitter (caffeine), and umami (monosodium glutamate, MSG) in a 44 year old female PWCA. Five concentration levels (three for salty) were tested in triplicate for each stimulus. A nose clip was used to exclude contribution by olfactory detection. Contingency tables were constructed to determine relationships between identification accuracy and stimulus or concentration level.
Results
The sweet (17.1 g/L), salty (0.58 g/L), and bitter (0.02 g/L) stimuli were detected at comparable concentrations to those reported in non-randomized trials, while sour (0.02 g/L) was detected at a lower concentration. The most common substitution was salty for umami (n = 7). Identification accuracy was significantly associated with taste stimuli χ2 = 12.634, p = 0.013. Concentration level was significantly associated with identification accuracy only for salty, χ2 = 9.000, p = 0.011.
Conclusion
This study has demonstrated the perception of different tastes in a PWCA. This is the first known report of umami being identified as a unique taste in a PWCA. Variations in threshold taste concentrations compared to normal individuals indicate certain gustatory dysfunction.
doi:10.1016/j.jobcr.2014.08.001
PMCID: PMC4252641  PMID: 25737929
Congenital; Aglossia; Taste; Gustation; Umami
21.  Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions 
There has been an increasing interest in the study of the innate immune system in recent years. However, few studies have focused on whether innate immunity can acquire tolerance. Therefore, in this study, we investigated tolerance in the innate immune system via the consecutive weekly and daily injections of emulsions modified with polyethylene glycol (PEG), referred to as PEGylated emulsions (PE). The effects of these injections of PE on pharmacokinetics and biodistribution were studied in normal and macrophage-depleted rats. Additionally, we evaluated the antigenic specificity of immunologic tolerance. Immunologic tolerance against PE developed after 21 days of consecutive daily injections or the fourth week of PE administration. Compared with a single administration, it was observed that the tolerant rats had a lower rate of PE clearance from the blood, which was independent of the stress response. In addition, weekly PE injections caused injury to the spleen. Furthermore, the rats tolerant to PEs with the methoxy group (–OCH3) of PEG, failed to respond to the PEs with a different terminal group of PEG or to non-PEG emulsions. Innate immunity tolerance was induced by PE, regardless of the mode of administration. Further study of this mechanism suggested that monocytes play an essential role in the suppression of innate immunity. These findings provide novel insights into the understanding of the innate immune system.
doi:10.2147/IJN.S66318
PMCID: PMC4128795  PMID: 25120362
immunologic tolerance; innate immune system; pharmacokinetics; biodistribution; antigenic specificity
22.  Oral Immunization with Escherichia coli Expressing a Lipidated Form of LigA Protects Hamsters against Challenge with Leptospira interrogans Serovar Copenhageni 
Infection and Immunity  2014;82(2):893-902.
Leptospirosis is a potentially fatal zoonosis transmitted by reservoir host animals that harbor leptospires in their renal tubules and shed the bacteria in their urine. Leptospira interrogans serovar Copenhageni transmitted from Rattus norvegicus to humans is the most prevalent cause of urban leptospirosis. We examined L. interrogans LigA, domains 7 to 13 (LigA7-13), as an oral vaccine delivered by Escherichia coli as a lipidated, membrane-associated protein. The efficacy of the vaccine was evaluated in a susceptible hamster model in terms of the humoral immune response and survival from leptospiral challenge. Four weeks of oral administration of live E. coli expressing LigA7-13 improved survival from intraperitoneal (i.p.) and intradermal (i.d.) challenge by L. interrogans serovar Copenhageni strain Fiocruz L1-130 in Golden Syrian hamsters. Immunization with E. coli expressing LigA7-13 resulted in a systemic antibody response, and a significant LigA7-13 IgG level after the first 2 weeks of immunization was completely predictive of survival 28 days after challenge. As in previous LigA vaccine studies, all immunized hamsters that survived infection had renal leptospiral colonization and histopathological changes. In summary, an oral LigA-based vaccine improved survival from leptospiral challenge by either the i.p. or i.d. route.
doi:10.1128/IAI.01533-13
PMCID: PMC3911400  PMID: 24478102
23.  Cooperation with both synergistic and local interactions can be worse than each alone 
Scientific Reports  2014;4:5536.
Cooperation is ubiquitous ranging from multicellular organisms to human societies. Population structures indicating individuals' limited interaction ranges are crucial to understand this issue. But it remains unknown to what extend multiple interactions involving nonlinearity in payoff influence the cooperation in structured populations. Here we show a rule, which determines the emergence and stabilization of cooperation, under multiple discounted, linear, and synergistic interactions. The rule is validated by simulations in homogenous and heterogenous structured populations. We find that the more neighbours there are the harder for cooperation to evolve for multiple interactions with linearity and discounting. For synergistic scenario, however, distinct from its pairwise counterpart, moderate number of neighbours can be the worst, indicating that synergistic interactions work with strangers but not with neighbours. Our results suggest that the combination of different factors which promotes cooperation alone can be worse than that with every single factor.
doi:10.1038/srep05536
PMCID: PMC4078301  PMID: 24985887
24.  Penicillium fusisporum and P. zhuangii, Two New Monoverticillate Species with Apical-Swelling Stipes of Section Aspergilloides Isolated from Plant Leaves in China 
PLoS ONE  2014;9(7):e101454.
Two new Penicillium species isolated from plant leaves are reported here, namely, P. fusisporum (type strain AS3.15338T = NRRL 62805T = CBS 137463T) and P. zhuangii (type strain AS3.15341T = NRRL 62806T = CBS 137464T). P. fusisporum is characterized by fast growth rate, apical-swelling monoverticillate penicilli, verrucose stipes, fusiform to oblong conidia about 3.5–4×2–2.5 µm and cinnamon-colored sclerotia. While P. zhuangii presents a moderate growth rate, it also bears apical-swelling monoverticillate penicilli but its stipes are smooth-walled, and produces ovoid to globose smooth-walled conidia about 3–3.5 µm. Both species belong to section Aspergilloides, and P. fusisporum is related to “P. thomii var. flavescens”, while P. zhuangii is morphologically similar to P. lividum. Phylogenetic analyses of sequences of calmodulin and beta-tubulin genes both show that the two new taxa form distinct monophyletic clades.
doi:10.1371/journal.pone.0101454
PMCID: PMC4079715  PMID: 24988489
25.  Bluffing promotes overconfidence on social networks 
Scientific Reports  2014;4:5491.
The overconfidence, a well-established bias, in fact leads to unrealistic expectations or faulty assessment. So it remains puzzling why such psychology of self-deception is stabilized in human society. To investigate this problem, we draw lessons from evolutionary game theory which provides a theoretical framework to address the subtleties of cooperation among selfish individuals. Here we propose a spatial resource competition model showing that, counter-intuitively, moderate values rather than large values of resource-to-cost ratio boost overconfidence level most effectively. In contrast to theoretical results in infinite well-mixed populations, network plays a role both as a “catalyst” and a “depressant” in the spreading of overconfidence, especially when resource-to-cost ratio is in a certain range. Moreover, when bluffing is taken into consideration, overconfidence evolves to a higher level to counteract its detrimental effect, which may well explain the prosperity of this “erroneous” psychology.
doi:10.1038/srep05491
PMCID: PMC4074791  PMID: 24974793

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